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Grp  -  gastrin releasing peptide

Mus musculus

Synonyms: BLP, GRP, Gastrin-releasing peptide
 
 
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Disease relevance of Grp

 

Psychiatry related information on Grp

  • In the present study we evaluated the effects of the BN/gastrin-releasing peptide receptor (GRP) antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) bombesin (6-14) (RC-3095) on apomorphine and MK-801-induced stereotyped behavior in mice [5].
  • In Experiment 1, the drug scopolamine (1 or 2 mg/kg, ip) was used to induce amnesia prior to training, and GRP (32 nmol/kg, ip) or saline (control) was administered immediately after training [6].
  • Posttraining administration of gastrin-releasing peptide improves memory loss in scopolamine- and hypoxia-induced amnesic mice [6].
 

High impact information on Grp

  • We identified the Grp gene, encoding gastrin-releasing peptide, as being highly expressed both in the lateral nucleus of the amygdala, the nucleus where associations for Pavlovian learned fear are formed, and in the regions that convey fearful auditory information to the lateral nucleus [7].
  • Earlier studies have shown that GRP and NMB are expressed in different regions of both the CNS and peripheral organs [8].
  • Bombesin or gastrin-releasing peptide had no effect on the growth of estrogen-independent tumors [4].
  • Single intravenous infusions of 2A11 (20 mg/20-25-kg dogs) into normal mongrel dogs with surgically created gastric fistulas antagonized the stimulatory effects of exogenously infused gastrin-releasing peptide or bombesin on plasma gastrin release and gastric acid secretion [9].
  • The density and distribution of the various peptide-containing fibers did not differ overtly between the pyloric and oxyntic gland areas except for the GRP fibers, which were fewer in the pyloric than in the oxyntic mucosa [10].
 

Chemical compound and disease context of Grp

  • In this report, we demonstrate that both GRP and another member of the bombesin family of peptides, neuromedin B (NMB), are also autocrine growth factors for non-small cell lung carcinoma (NSCLC) [11].
  • Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with a [D-Trp6] agonist of luteinizing hormone releasing hormone (LH-RH), somatostatin analogue (RC-160), and bombesin/gastrin releasing peptide antagonist (RC-3095) [12].
  • Antagonists of bombesin/gastrin-releasing peptide inhibit growth of SW-1990 human pancreatic adenocarcinoma and production of cyclic AMP [13].
  • We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier [14].
  • The liver injury was induced by either an injection of antibasic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum (C. parvum) pretreated DDY mice [15].
 

Biological context of Grp

 

Anatomical context of Grp

  • The relative potencies of a series of GRP analogs for the soluble receptor and intact membranes indicated that the extraction procedure did not significantly alter the receptor's ligand binding specificity [21].
  • The cross-linking agent ethyleneglycolbis(succinimidylsuccinate) covalently linked 125I-GRP to a single Mr 75 000-85 000 protein in membrane preparations of 3T3 cells [22].
  • In contrast to the gastrin-releasing peptide (GRP)-preferring subtype, which has been widely studied, nothing is known about the cellular mechanisms of the neuromedin B (NMB)-preferring subtype, which occurs widely in the central nervous system and gastrointestinal tissues, partially because of the lack of a cell line with functional receptors [23].
  • To investigate whether smaller GRP fragments could bind to the GRP receptor without stimulating mitogenesis, we performed binding inhibition and thymidine uptake assays with Swiss 3T3 fibroblasts [24].
  • Under conditions found optimal for binding, it is demonstrated that 125I-labeled gastrin-releasing peptide can be cross-linked specifically to a glycoprotein of apparent molecular mass of 65,000 daltons on the surface of the NIH-3T3 cells [25].
 

Associations of Grp with chemical compounds

  • GRP had the same effects as bombesin, whereas neither NMB nor a synthetic bombesin receptor type 3 ligand had any effect [1].
  • Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice [26].
  • Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity [27].
  • The number and affinity of bombesin/GRP receptor sites and modulation of 125I-GRP binding by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) are unaffected in membrane preparations from vasopressin-treated cultures [20].
  • For Bn receptor agonists the relative potencies were: NMB (1.7 nM) approximately equal to litorin (3 nM) greater than ranatensin (8 nM) greater than Bn (19 nM) greater than neuromedin C (NMC) (210 nM) greater than GRP (500 nM) [23].
 

Physical interactions of Grp

 

Regulatory relationships of Grp

 

Other interactions of Grp

  • We now demonstrate that GRP and GRP receptor genes are expressed in fetal mouse lung as early as embryonic day 12 (E12), when lung buds are beginning to branch [16].
  • In the reverse study using gain-of-affinity NMBR chimeras, only replacement of EC3 of NMBR markedly increased GRP affinity [33].
  • These results were confirmed by making the reverse mutations in BRS-3 to make GRP gain of affinity mutants [18].
  • Our present studies suggest that GRP neurons in the retinorecipient ventral area of the SCN convey the photic entrainable signals from the ventral SCN to the dorsal SCN via induction of the mPer gene [34].
  • Furthermore, neither GRP or CCK seems involved in the insulin and glucagon response to 2-DG in the mouse [35].
 

Analytical, diagnostic and therapeutic context of Grp

References

  1. Bombesin inhibits alveolarization and promotes pulmonary fibrosis in newborn mice. Ashour, K., Shan, L., Lee, J.H., Schlicher, W., Wada, K., Wada, E., Sunday, M.E. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  2. Inhibition of growth of OV-1063 human epithelial ovarian cancers and c- jun and c- fos oncogene expression by bombesin antagonists. Chatzistamou, I., Schally, A.V., Sun, B., Armatis, P., Szepeshazi, K. Br. J. Cancer (2000) [Pubmed]
  3. Generation and characterization of mice lacking gastrin-releasing peptide receptor. Wada, E., Watase, K., Yamada, K., Ogura, H., Yamano, M., Inomata, Y., Eguchi, J., Yamamoto, K., Sunday, M.E., Maeno, H., Mikoshiba, K., Ohki-Hamazaki, H., Wada, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  4. Growth inhibition of estrogen-dependent and estrogen-independent MXT mammary cancers in mice by the bombesin and gastrin-releasing peptide antagonist RC-3095. Szepeshazi, K., Schally, A.V., Halmos, G., Groot, K., Radulovic, S. J. Natl. Cancer Inst. (1992) [Pubmed]
  5. The bombesin/gastrin releasing peptide receptor antagonist RC-3095 blocks apomorphine but not MK-801-induced stereotypy in mice. Meller, C.A., Henriques, J.A., Schwartsmann, G., Roesler, R. Peptides (2004) [Pubmed]
  6. Posttraining administration of gastrin-releasing peptide improves memory loss in scopolamine- and hypoxia-induced amnesic mice. Santo-Yamada, Y., Yamada, K., Wada, K. Physiol. Behav. (2001) [Pubmed]
  7. Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Shumyatsky, G.P., Tsvetkov, E., Malleret, G., Vronskaya, S., Hatton, M., Hampton, L., Battey, J.F., Dulac, C., Kandel, E.R., Bolshakov, V.Y. Cell (2002) [Pubmed]
  8. Two distinct receptor subtypes for mammalian bombesin-like peptides. Battey, J., Wada, E. Trends Neurosci. (1991) [Pubmed]
  9. Preclinical evaluation of an anti-autocrine growth factor monoclonal antibody for treatment of patients with small-cell lung cancer. Avis, I.L., Kovacs, T.O., Kasprzyk, P.G., Treston, A.M., Bartholomew, R., Walsh, J.H., Cuttitta, F., Mulshine, J.L. J. Natl. Cancer Inst. (1991) [Pubmed]
  10. Peptide-containing nerve fibers in the stomach wall of rat and mouse. Ekblad, E., Ekelund, M., Graffner, H., Håkanson, R., Sundler, F. Gastroenterology (1985) [Pubmed]
  11. Evidence for autocrine actions of neuromedin B and gastrin-releasing peptide in non-small cell lung cancer. Siegfried, J.M., Krishnamachary, N., Gaither Davis, A., Gubish, C., Hunt, J.D., Shriver, S.P. Pulmonary pharmacology & therapeutics. (1999) [Pubmed]
  12. Inhibition of growth of HT-29 human colon cancer xenografts in nude mice by treatment with bombesin/gastrin releasing peptide antagonist (RC-3095). Radulovic, S., Miller, G., Schally, A.V. Cancer Res. (1991) [Pubmed]
  13. Antagonists of bombesin/gastrin-releasing peptide inhibit growth of SW-1990 human pancreatic adenocarcinoma and production of cyclic AMP. Qin, Y., Ertl, T., Cai, R.Z., Horvàth, J.E., Groot, K., Schally, A.V. Int. J. Cancer (1995) [Pubmed]
  14. Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215. Szereday, Z., Schally, A.V., Nagy, A., Plonowski, A., Bajo, A.M., Halmos, G., Szepeshazi, K., Groot, K. Br. J. Cancer (2002) [Pubmed]
  15. Effect of OKY-046 and ONO-3708 on liver injury in mice. Nagai, H., Aoki, M., Shimazawa, T., Yakuo, I., Koda, A., Kasahara, M. Jpn. J. Pharmacol. (1989) [Pubmed]
  16. Bombesin and [Leu8]phyllolitorin promote fetal mouse lung branching morphogenesis via a receptor-mediated mechanism. King, K.A., Torday, J.S., Sunday, M.E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  17. Bombesin-like peptide receptor gene expression, regulation, and function in fetal murine lung. Shan, L., Emanuel, R.L., Dewald, D., Torday, J.S., Asokanathan, N., Wada, K., Wada, E., Sunday, M.E. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  18. Identification of key amino acids in the gastrin-releasing peptide receptor (GRPR) responsible for high affinity binding of gastrin-releasing peptide (GRP). Nakagawa, T., Hocart, S.J., Schumann, M., Tapia, J.A., Mantey, S.A., Coy, D.H., Tokita, K., Katsuno, T., Jensen, R.T. Biochem. Pharmacol. (2005) [Pubmed]
  19. Gastrointestinal peptide signalling in health and disease. Rozengurt, E., Guha, S., Sinnett-Smith, J. The European journal of surgery. Supplement. : = Acta chirurgica. Supplement. (2002) [Pubmed]
  20. Arachidonic acid release by bombesin. A novel postreceptor target for heterologous mitogenic desensitization. Millar, J.B., Rozengurt, E. J. Biol. Chem. (1990) [Pubmed]
  21. Purification and characterization of the bombesin/gastrin-releasing peptide receptor from Swiss 3T3 cells. Feldman, R.I., Wu, J.M., Jenson, J.C., Mann, E. J. Biol. Chem. (1990) [Pubmed]
  22. Bombesin receptor in membranes from Swiss 3T3 cells. Binding characteristics, affinity labelling and modulation by guanine nucleotides. Sinnett-Smith, J., Lehmann, W., Rozengurt, E. Biochem. J. (1990) [Pubmed]
  23. Activation of neuromedin B-preferring bombesin receptors on rat glioblastoma C-6 cells increases cellular Ca2+ and phosphoinositides. Wang, L.H., Battey, J.F., Wada, E., Lin, J.T., Mantey, S., Coy, D.H., Jensen, R.T. Biochem. J. (1992) [Pubmed]
  24. Minimal ligand analysis of gastrin releasing peptide. Receptor binding and mitogenesis. Heimbrook, D.C., Boyer, M.E., Garsky, V.M., Balishin, N.L., Kiefer, D.M., Oliff, A., Riemen, M.W. J. Biol. Chem. (1988) [Pubmed]
  25. Identification of the bombesin receptor on murine and human cells by cross-linking experiments. Kris, R.M., Hazan, R., Villines, J., Moody, T.W., Schlessinger, J. J. Biol. Chem. (1987) [Pubmed]
  26. Islet function phenotype in gastrin-releasing peptide receptor gene-deficient mice. Persson, K., Pacini, G., Sundler, F., Ahrén, B. Endocrinology (2002) [Pubmed]
  27. Comparison of the peptide structural requirements for high affinity interaction with bombesin receptors. Lin, J.T., Coy, D.H., Mantey, S.A., Jensen, R.T. Eur. J. Pharmacol. (1995) [Pubmed]
  28. G alpha 12 and G alpha 13 stimulate Rho-dependent stress fiber formation and focal adhesion assembly. Buhl, A.M., Johnson, N.L., Dhanasekaran, N., Johnson, G.L. J. Biol. Chem. (1995) [Pubmed]
  29. Gastrin-releasing peptide promotes suprachiasmatic nuclei cellular rhythmicity in the absence of vasoactive intestinal polypeptide-VPAC2 receptor signaling. Brown, T.M., Hughes, A.T., Piggins, H.D. J. Neurosci. (2005) [Pubmed]
  30. Gastrin releasing peptide (GRP): effects on basal and stimulated insulin and glucagon secretion in the mouse. Pettersson, M., Ahrén, B. Peptides (1987) [Pubmed]
  31. Protein kinase C-dependent activation of a myelin basic protein kinase by gastrin-releasing peptide in Swiss 3T3 fibroblasts. Hansson, A. Cell. Signal. (1991) [Pubmed]
  32. Distinguishing bombesin receptor subtypes using the oocyte assay. Shapira, H., Wada, E., Battey, J.F., Jensen, R.T., Coy, D.H., Kusano, K. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  33. Molecular basis of the selectivity of gastrin-releasing peptide receptor for gastrin-releasing peptide. Tokita, K., Hocart, S.J., Coy, D.H., Jensen, R.T. Mol. Pharmacol. (2002) [Pubmed]
  34. Gastrin-releasing peptide mediates photic entrainable signals to dorsal subsets of suprachiasmatic nucleus via induction of Period gene in mice. Aida, R., Moriya, T., Araki, M., Akiyama, M., Wada, K., Wada, E., Shibata, S. Mol. Pharmacol. (2002) [Pubmed]
  35. Peptide receptor antagonists in the study of insulin and glucagon secretion in mice. Karlsson, S., Ahrén, B. Eur. J. Pharmacol. (1990) [Pubmed]
  36. Diurnal regulation of the gastrin-releasing peptide receptor in the mouse circadian clock. Karatsoreos, I.N., Romeo, R.D., McEwen, B.S., Silver, R. Eur. J. Neurosci. (2006) [Pubmed]
  37. Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is critical for the high selectivity of the peptoid antagonist PD168368. Tokita, K., Hocart, S.J., Katsuno, T., Mantey, S.A., Coy, D.H., Jensen, R.T. J. Biol. Chem. (2001) [Pubmed]
  38. Effective inhibition of experimental human ovarian cancers with a targeted cytotoxic bombesin analogue AN-215. Engel, J.B., Keller, G., Schally, A.V., Halmos, G., Hammann, B., Nagy, A. Clin. Cancer Res. (2005) [Pubmed]
 
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